Pathogenesis of autoimmunity in alphabeta T cell-deficient lupus-prone mice.
Pathogenesis of autoimmunity in alphabeta T cell-deficient lupus-prone mice.
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Alphata T 细胞缺陷型狼疮易感小鼠自身免疫的发病机制。
DOI：
10.1046/j.1365-2249.1998.00424.x
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发表时间：
1998
影响因子：
4.6
通讯作者：
Craft,J
中科院分区：
文献类型：
--
作者：
Peng,SL;Cappadona,J;McNiff,JM;Madaio,MP;Owen,MJ;Hayday,AC;Craft,J
MRL小鼠中的鼠狼疮强烈归因于αβ T细胞依赖性机制。非αβ T细胞依赖性机制，如γδ T细胞，已被证明可以驱动抗体和自身抗体的产生，但它们并不被认为能够诱导终末器官疾病。在这里，我们通过检查通过γδ T细胞和/或非αβ T细胞依赖性机制可获得的终末器官疾病的机制和程度，在具有功能性或缺陷性Fas抗原（Fas + orlpr）的TCR α−/− MRL小鼠中评估两种原型狼疮病变，肾脏和皮肤疾病，扩展了这些先前工作的发现。观察到1岁时，TCR α−/− MRL小鼠发生疾病，其特征为死亡率增加、明显的肾脏疾病和皮肤病变。虽然与TCR α+/+ MRL/lpr动物相比，αβ T细胞缺陷动物的肾脏和皮肤病变的发病延迟和/或严重程度降低，但与年龄匹配的对照非自身免疫小鼠相比，肾脏和皮肤病变的严重程度明显增加。与TCR α+/+ MRL小鼠（其疾病反映了泛同种型免疫复合物沉积伴显著补体结合）相反，TCR α−/− MRL动物的肾脏疾病主要反映了IgG 1免疫复合物沉积伴补体结合不良。因此，本研究最终证明，非αβ T细胞依赖性机制可诱导小鼠狼疮的肾脏和皮肤损伤，但至少在肾脏中，仅通过相对非病理性同种型的体液自身免疫，导致终末器官损伤延迟发作。
Murine lupus in MRL mice has been strongly attributed to αβ T cell‐dependent mechanisms. Non‐αβ T cell‐dependent mechanisms, such as γδ T cells, have been shown to drive antibody and autoantibody production, but they have not been considered capable of inducing end‐organ disease. Here, we have expanded upon the findings of such previous work by examining the mechanism and extent of end‐organ disease attainable via γδ T cells and/or non‐αβ T cell‐dependent mechanisms, assessing two prototypical lupus lesions, renal and skin disease, in TCR α−/− MRL mice that possessed either functional or defective Fas antigen (Fas + orlpr). Observed to 1 year of age, TCR α−/− MRL mice developed disease characterized by increased mortality, overt renal disease and skin lesions. While delayed in onset and/or reduced in severity compared with TCR α+/+ MRL/lpranimals, renal and skin lesions in αβ T cell‐deficient animals were clearly increased in severity compared with age‐matched control non‐autoimmune mice. In contrast to TCR α+/+ MRL mice, whose disease reflected pan‐isotype immune complex deposition with significant complement fixation, renal disease in TCR α−/− MRL animals reflected predominantly IgG1 immune complex deposition, with poor complement fixation. Thus, this study demonstrates conclusively that non‐αβ T cell‐dependent mechanisms can induce renal and skin injury in murine lupus, but at least in the kidney, only via humoral autoimmunity of a relatively non‐pathological isotype which results in the delayed onset of end‐organ damage.